Influence of vein valves in the development of arteriosclerosis in venoarterial grafts in the rabbit

Abstract

Coronary saphenous vein grafts in human beings have a more limited long-term patency rate than internal thoracic artery grafts, primarily because of more rapid development of arteriosclerosis. The factors responsible for this increased susceptibility are not completely understood. To test the hypothesis that vein valves may influence this process, we studied 48 hypercholesterolemic rabbits with jugular vein grafts interposed into the carotid arterial circulation. In 24 animals (group A), the vein segments did not contain a vein valve. In the other 24 animals (group B), a vein valve was present. Both groups were further divided in four subgroups of six to be put to death at 2, 4, 6, and 8 weeks after the operation. All animals were fed a 2% cholesterol diet. At postmortem examination, alternate 2 mm sections were either stained with hematoxylin and eosin for histologic and morphometric studies or frozen in liquid nitrogen for immunohistochemistry and in situ hybridization studies. Proliferating cell nuclear antigen immunostaining was used to study cell proliferation. Wall thickness of vein grafts increased with time. During the first 2 weeks intimal and medial thickening was primarily due to an increase in numbers of cells. Between 2 and 6 weeks further intimal and medial thickening occurred, but without additional increase in cell numbers. After 6 weeks, foam cells and lipid deposits started to appear. By 8 weeks, changes identical to those seen in arteriosclerotic plaques in human beings were evident. These changes developed sooner and with more intensity in group B animals (p < 0.01 to 0.001), and they developed faster and with more severity in segments of vein located distal to the valve than in the segments located proximal to the valve (p < 0.001). This is the first controlled experiment demonstrating that the presence of valves in the vein segments is associated with augmented and accelerated intimal changes leading to vein atheromatosis.

Prolonged hypercholesterolemia-induced tissue factor expression in rabbit vein grafts: a potential mechanism for graft failure

“…Vessel wall edema and fibrin deposition on a partially disrupted endothelium were seen. Implanted vein grafts became progressively hyperplastic as time elapsed, with maximal thickness seen at 6-8 weeks as reported earlier [14]. Thickness increase in the early stage was mostly due to proliferation of vascular smooth muscle cells, whereas in the later phase it was because of extracellular matrix elaboration with few cells.…”

“…Autologous jugular vein grafts were implanted in the common carotid artery under general anesthesia with ketamine and xylazine as described earlier [14], after systemic heparinization (3 mg/kg) the external jugular vein was exposed on one side of the neck, removed, flushed with heparinized saline, and marked for orientation. The carotid artery was exposed, clamped, and end-to-side anastomoses to both ends of reversed vein graft were performed with continuous 8-0 polypropylene sutures, after which the carotid artery was tied and divided.…”

Subendothelial Proteoglycan Synthesis and Transforming Growth Factor Beta Distribution Correlate with Susceptibility to Atherosclerosis

“…Several intirinsic dif ferences between the ITA and SV, however, have also been postulated to be important in determining suscepti bility to atherosclerosis. These factors include (1) differ ences in the number of fenestrations in the internal elastic lamina [6]; (2) differences in prostacyclin and nitric oxide production by the endothelium [5]: (3) structural differ ences in the attachment of endothelium [7]; (4) the pres ence of valves in SV [8], and (5), most relevant to this study, biochemical differences in the proteoglycan com position of the arterial wall [9].…”

Distribution of Saphenous Vein Valves and Its Pratical Importance

“…This vessel remains an essential component in strategies for coronary artery bypass grafting in humans. The vessel is used alone or in combination with arterial grafts and has the advantage of being available autologous vascular tissue in most patients in need of such surgeries [ 1 ] . Its use in composite graft with the left internal thoracic artery (LITA) could allow complete revascularization of the left coronary system (LCS) without a cardiopulmonary bypass (CPB) and without ascending aorta (MAA) in order to reduce some risks and complications in the immediate postoperative period.…”